Uric Acid Concentration, Serum, Quantitative Trait Locus 4

A number sign (#) is used with this entry because serum uric acid concentration and susceptibility to gout-4 can be conferred by variation in the SLC17A3 gene (611034) on chromosome 6p21.

For a phenotypic description of gout and a discussion of genetic heterogeneity of serum uric acid concentration quantitative trait loci, see UAQTL1 (138900).

Mapping

By genomewide linkage analysis of 7,699 participants in the Framingham cohort, Dehghan et al. (2008) found a significant association between serum uric acid concentration and rs1165205 in intron 1 of the SLC17A3 gene (611034) on chromosome 6p21 (p 5.6 x 10(-10)). The locus showed linkage disequilibrium extending downstream to include the SLC17A1 (182308) and SLC17A4 (604216) genes. The findings were replicated in 11,024 white individuals in the ARIC cohort, yielding a p value of 8.4 x 10(-11). For white individuals from the Framingham, ARIC, and Rotterdam cohorts, the combined p value was 3.8 x 10(-29), and further analysis showed that the SNP was also associated with the development of gout in white participants (odds ratio of 0.85; p = 2.0 x 10(-3)). SNP rs1165205 did not show significant association with serum uric acid concentration or gout in 3,843 black individuals from the ARIC cohort or 4,148 participants in the Rotterdam cohort.

Molecular Genetics

In 2 unrelated Japanese men in their sixties with hyperuricemia and gout, respectively, Jutabha et al. (2010) identified 2 different heterozygous missense mutations in the SLC17A3 gene (611034.0001 and 611034.0002). Each mutation caused reduced urate efflux compared to wildtype when expressed in Xenopus oocytes.